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Most prior studies have focused on individual\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      -by-biomarker interactions rather than the broader conditional dependency structure among metabolic variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      We aimed to examine whether\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 is conditionally connected to metabolic factors and whether network architecture differs by genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In 2454 participants from the Korean Longitudinal Study on Cognitive Aging and Dementia with complete data on 13 variables, conditional dependency networks were estimated using graphical least absolute shrinkage and selection operator models and mixed graphical models. Network Comparison Tests were used to compare 12-node metabolic networks between \u03b54 carriers and non-carriers. Cox proportional hazards models evaluated whether hub biomarkers predicted incident cognitive impairment over a median follow-up of 7.4 years and whether associations differed by\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 showed negligible conditional connectivity, with near-zero partial correlations in GLASSO (maximum |r|\u2009=\u20090.0114) and zero edge weights in mixed graphical models. The 12-node metabolic network did not differ significantly between carriers and non-carriers in either network structure (M\u2009=\u20090.1671, p\u2009=\u20090.45) or global strength (S\u2009=\u20092.3662, p\u2009=\u20090.46). Among 1922 baseline cognitively normal participants, 504 developed cognitive impairment during follow-up. Neither the\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u00d7 homocysteine interaction (p\u2009=\u20090.921) nor the\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u00d7 creatinine interaction (p\u2009=\u20090.402) was significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 was conditionally independent of the peripheral metabolic variables examined, with no major genotype-specific differences in network architecture. These findings highlight the importance of metabolic dementia prevention regardless of genotype, although interventional confirmation is warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261476718","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:47:00Z","timestamp":1787921220000},"page":"1335-1346","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>APOE<\/i>\n                    \u03b54 and peripheral metabolic network architecture in older adults"],"prefix":"10.1177","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-3490","authenticated-orcid":false,"given":"Dae Jong","family":"Oh","sequence":"first","affiliation":[{"name":"Seoul National University Bundang 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